Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis.
Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis.
复制标题
DOI：
10.1016/j.ajog.2015.01.017
复制
发表时间：
2015-06
影响因子：
9.8
通讯作者：
Yang, Peixin
中科院分区：
文献类型：
--
作者：
Wu, Yanqing;Wang, Fang;Reece, E. Albert;Yang, Peixin
关键词：
姜黄素是一种天然存在的多酚，存在于姜黄植物（姜黄）的根部，具有抗氧化，抗肿瘤和抗炎特性。在这里，我们测试姜黄素治疗是否减少高葡萄糖诱导的神经管缺陷（NTDs），如果这是通过阻断细胞应激和半胱天冬酶激活而发生的。收集胚胎第8.5天的小鼠胚胎，用于在正常葡萄糖（100 mg/dl葡萄糖）或高葡萄糖（300 mg/dl葡萄糖）条件下，用或不用姜黄素处理的全胚胎培养。培养24 h后，测定胚胎中氧化应激标记物、亚硝化应激标记物、内质网（ER）应激标记物、切割的半胱天冬酶3和8的蛋白水平以及脂质过氧化物（LPO）水平。培养36小时后，检查胚胎是否有NTD形成的证据。虽然10 μM姜黄素没有显著降低高糖引起的NTD的发生率，但20 μM姜黄素显著改善高糖诱导的NTD形成。姜黄素抑制在高糖条件下培养的胚胎的氧化应激。治疗降低了脂质过氧化标记物4-羟基壬烯醛（4-HNE）、硝基酪氨酸修饰蛋白和LPO的水平。姜黄素还通过抑制磷酸化蛋白激酶核糖核酸（RNA）样ER激酶（p-PERK）、磷酸化肌醇需要蛋白-1 α（p-IRE 1 α）、磷酸化真核起始因子2α（p-eIF 2 α）、C/EBP同源蛋白（CHOP）、结合免疫球蛋白（BiP）和x-box结合蛋白1（XBP 1）mRNA剪接来阻断ER应激。此外，姜黄素废除在高糖条件下培养的胚胎中的半胱天冬酶3和半胱天冬酶8裂解。姜黄素通过阻断细胞应激和半胱天冬酶激活来减少高糖诱导的NTD形成，这表明姜黄素补充剂可以减少糖尿病对胚胎的负面影响。需要进一步的研究来确定实验结果是否可以转化为临床环境。
Curcumin is a naturally occurring polyphenol present in the roots of the Curcuma longa plant (turmeric), which possesses antioxidant, anti-tumorigenic and anti-inflammatory properties. Here, we test whether curcumin treatment reduces high glucose-induced neural tube defects (NTDs), and if this occurs via blocking cellular stress and caspase activation. Embryonic day 8.5 mouse embryos were collected for use in whole embryo culture under normal glucose (100 mg/dl glucose) or high glucose (300 mg/dl glucose) conditions, with or without curcumin treatment. After 24 h in culture, protein levels of oxidative stress makers, nitrosative stress makers, endoplasmic reticulum (ER) stress makers, cleaved caspase 3 and 8 and the level of lipid peroxides (LPO) were determined in the embryos. After 36 h in culture, embryos were examined for evidence of NTD formation. Although 10 μM curcumin did not significantly reduce the rate of NTDs caused by high glucose, 20 μM curcumin significantly ameliorated high glucose-induced NTD formation. Curcumin suppressed oxidative stress in embryos cultured under high glucose conditions. Treatment reduced the levels of the lipid peroxidation marker, 4-hydroxynonenal(4-HNE), nitrotyrosine-modified protein, and LPO. Curcumin also blocked ER stress by inhibiting phosphorylated protein kinase ribonucleic acid (RNA)-like ER kinase (p-PERK), phosphorylated inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP) and x-box binding protein 1 (XBP1) mRNA splicing. Additionally, curcumin abolished caspase 3 and caspase 8 cleavage in embryos cultured under high glucose conditions. Curcumin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation, suggesting that curcumin supplements could reduce the negative effects of diabetes on the embryo. Further investigation will be needed to determine if the experimental findings can translate into clinical settings.
登录
查看更多内容
影响因子：
9.8
作者：
Correa, Adolfo;Gilboa, Suzanne M.;Reece, E. Albert
通讯作者：
Reece, E. Albert
影响因子：
4.5
作者：
Farhangkhoee, Hana;Khan, Zia A;Chen, Shali;Chakrabarti, Subrata
通讯作者：
Chakrabarti, Subrata
影响因子：
9.8
作者：
Acosta, Ometeotl;Ramirez, Vanessa I.;Jansson, Thomas
通讯作者：
Jansson, Thomas
影响因子：
9.8
作者：
Ahmadzia, Homa Khorrami;Thomas, Samantha Marie;Boyd, Brita Katherine
通讯作者：
Boyd, Brita Katherine
影响因子：
5.5
作者：
Chhunchha, Bhavana;Fatma, Nigar;Singh, Dhirendra P.
通讯作者：
Singh, Dhirendra P.